Diabetes is a condition characterized by abnormal insulin secretion and a variety of metabolic and vascular manifestations reflected in a tendency toward inappropriately elevated blood glucose levels and which if left poorly treated or untreated can result in accelerated, nonspecific atherosclerosis, neuropathy and thickened capillary lamina causing renal and retinal impairment. Diabetes is characterized as being insulin dependent (Type I) and non-insulin dependent (Type II). Type I diabetes is due to damage and eventual loss of the .beta.-cells of the pancreatic islets of Langerhans with a resulting loss of insulin production. Type II diabetics secrete insulin, however, the insulin is somehow not properly or effectively utilized in the metabolism of blood sugars and glucose accumulates in the blood to above normal levels. This condition is termed insulin resistance.
With the certainty of serious complications resulting from high glucose levels in poorly controlled or uncontrolled diabetics, means to lower blood glucose have been research goals for a considerable period of time. With Type I diabetes glucose control can, at present, only be achieved with daily insulin injections. With Type II diabetes glucose control can be effected from a combination of diet and drugs which lower glucose levels. The currently available oral hypoglycemic agents are not completely satisfactory since they may not offer complete blood glucose control or may provide a variety of undesirable side effects or they may elevate insulin concentrations to undesirable and dangerous levels. Thus, the search for improved oral hypo-glycemic agents is a continuing one.
The compounds of the present invention are piperazinylalkylpyrimidines. The literature discloses a number of piperazinylpyrimidines which are structurally distinct from the present compounds and generally have no disclosed hypoglycemic activity.
EP No. 115,714-A discloses 2-piperazinylpyrimidines of structural formula: ##STR2## where R.sup.1 =H or hydroxy; and R.sup.2 =H or C.sub.1-6 alkyl. These derivatives do not bear alkyl substituents on the pyrimidine ring and are structurally distinct from the instant compounds and have no disclosed hypoglycemic activity.
Japanese publication No. J5,0058 082 discloses piperazinylpyrimidines of structural formula: ##STR3## wherein R.sup.1 =H, alkyl, alkanoyl or PhCH.sub.2 ; and R is halo or R.sup.2 NH; R.sup.2 is H or alkyl. These substituted pyrimidines do not contain alkyl substituents directly bonded to the pyrimidine ring and are structurally distinct from the instant compounds.
U.S. Pat. No. 4,409,223 discloses 2-piperazinylpyrimidines of structural formula: ##STR4## These unalkylated pyrimidines, are structurally distinct from the instant compounds and have no disclosed hypoglycemic activity.
DE No. 3321969 discloses 2-piperazinylpyrimidines of structural formula ##STR5## wherein among other groups R.sup.1 =H or optionally substituted alkyl. These compounds were disclosed as intermediates in the further preparation of compounds substituted on the piperazine ring which have CNS activity.
U.S. Pat. No. 3,299,067 discloses 2-piperazinylpyrimidines of structural formula: ##STR6## wherein R is a benzyl or phenyl moiety, R.sup.1 is H or CH.sub.3, and X and Y among other groups are H or lower alkyl. These aryl substituted piperazinylpyrimidines are structurally distinct from the instant compounds.